Haemoglobinopathy

Question 1

describe the structure of a haemoglobin molecule

Answer 1

2 alpha globin chains
2 beta globin chains
one haem group (iron in porphyrin ring) per globin chain

Question 2

what are the major forms of Hb

Answer 2

HbA (2 alpha, 2 beta)
HbA2 (2 alpha, to delta)
HbF (2 alpha, 2 gamma)

Question 3

what is the most abundant type of haemoglobin in adults

Answer 3

HbA

Question 4

what chromosome are the genes for alpha globins on and how many are there

Answer 4

chromosome 16
2 alpha genes per chromosome
4 alpha genes per cell

Question 5

what chromosome are the genes for beta globins on and how many are there

Answer 5

chromosome 11
one beta gene per chromosome
2 genes per cell

Question 6

when do we express HbF as opposed to HbA

Answer 6

HbF - foetal Hb

Question 7

what are haemoglobinopathies

Answer 7

hereditary conditions affecting globin chain synthesis

Question 8

haemoglobinopathies are generally dominant/recessive disorders

Answer 8

autosomal recessive

Question 9

what is a thalassaemia

Answer 9

decreased rate of Hb synthesis (reduced or absent)

Question 10

what happens in structural haemoglobin variant disorders

Answer 10

production of structurally abnormal globin chains

Question 11

what are the 2 types of thalassaemias

Answer 11

alpha chain

beta chain

Question 12

what type of anaemia do thalassaemias cause

Answer 12

microcytic hypochromatic

Question 13

geographical risk factor for thalassaemia

Answer 13

tropical areas with high incidences of malaria

Question 14

what does the imbalance of globin chain within red cells cause

Answer 14

ineffective erythropoiesis and premature red cell death

Question 15

how many alpha genes are missing in a thal trait

Answer 15

one or two

Question 16

how many alpha genes are missing in HbH disease

Answer 16

3

Question 17

what is the condition where no functioning alpha genes

Answer 17

Hb Barts hydrops fetalis

Question 18

how would you differentiate thalassaemia from iron deficiency

Answer 18

both would be microcytic anaemia (low Hb, low MCV)

thalassaemia has a normal ferritin level with raised red cell count)

Question 19

clinical features of HbH disease

Answer 19

anaemia (possibly transfusion dependant)
splenomegaly
jaundice

Question 20

management of HbH disease

Answer 20

splenectomy

potentially transfusion if required

Question 21

clinical features of Hb Barts hydrops fetalis

Answer 21

severe anaemia 
cardiac failure 
growth retardation
hepatosplenomegaly 
die in utero

Question 22

how many faulty beta genes in B thalassaemia trait

Answer 22

one

Question 23

how many faulty beta genes in thalassaemia intermedia

Answer 23

two genes causing reduced B chain production
OR
one gene causing reduced B chain production and one causing no B chain production

Question 24

how many faulty beta chains in thalassaemia major

Answer 24

both genes causing no production of beta chains

Question 25

presentation of thalassaemia major

Answer 25

``` 6-24 months (when HbF falls off) pallor, failure to thrive hepatosplenomegaly skeletal changes organ damage ```

Question 26

management of thalassaemia major

Answer 26

transfusion monitor iron levels - prevent over-absorption bone marrow transplant if before complications

Question 27

consequences of iron overload

Answer 27

``` diabetes osteoporosis impaired growth cardiac disease liver disease ```

Question 28

management of iron overload

Answer 28

iron chelating drugs - desferrioxamine

Question 29

what causes sickle cell anaemia

Answer 29

point mutation on B globin gene causing HbS to be formed

Question 30

what happens to HbS if exposed to low O2 sats

Answer 30

polymerises - distorts cell membrane

Question 31

how many abnormal genes in sickle cell trait

Answer 31

1

Question 32

how many abnormal beta genes in sickle cell anaemia

Answer 32

2

Question 33

when may symptoms arise in sickle cell trait

Answer 33

severe hypoxia eg high altitude, under anaesthesia

Question 34

what is sickle crisis

Answer 34

episodes of tissue infarction due to vascular occlusion

Question 35

where is sickle crisis likely to occur

Answer 35

digits, bone marrow, lung, spleen, CNS

Question 36

what are some consequences of sickle cell anaemia

Answer 36

chronic haemolysis | hyposplenism (from multiple splenic infarcts)

Question 37

triggers of sickle crisis

Answer 37

``` hypoxia dehydration infection cold stress/disease ```

Question 38

management of sickle crises

Answer 38

``` opiate analgesia hydration rest O2 antibiotics (in infection) red cell transfusion if severe (neurological symptoms, chest crisis) ```

Question 39

long term management of sickle cell anaemia

Answer 39

reduce risk of infection - vaccines of encapsulated bacteria(pneumococcus, meningococcus, haemophilus) and prophylactic penicillin folic acid hydroxycarbamide (induces HbF production)

Question 40

what are investigations needed to detect haemoglobinopathy

Answer 40

FBC, Hb, red cell indices blood film high performance liquid chromatography/gel electrophoresis (looks at quantities of different Hb)

Question 41

what investigation is needed to confirm a thalassaemia trait

Answer 41

DNA testing